Crystal structures of complexes of a peptidic inhibitor with wild-type and two mutant HIV-1 proteases.

摘要: Crystal structures of the protease human immunodeficiency virus type 1 (HIV-1) and two mutant proteases, V82D V82N, have been determined. In all three cases enzyme forms a complex with peptidic inhibitor U-89360E. All determined to 2.3 A resolution satisfactory agreement factors: 0.173 for wild type, 0.175 V82D, 0.182 V82N. Comparison crystal provides explanations which are consistent known kinetic properties these enzymes U-89360E [Lin, Y., Lin, X., Hong, L., Foundling, S., Heinrikson, R. Thaisrivongs, Leelamanit, W., Raterman, D., Shah, M., Dunn, B.M., & Tang, J. (1995) Biochemistry 34, 1143-1152]. Unfavorable van der Waals interactions between mutated side chains at position 82 diminished affinity by enzymes. If mutation is potentially resistant an inhibitor, should not only increased Ki but also preserve considerable catalytic capability. The possesses qualities. structure, water molecule, connects flap missing or low occupancy. Absence this bridge may be important in determining Moreover, induces change polypeptide backbone regions, 35-41 67-68, related mobility.